Lecture 1: What is Pharmacology? Flashcards
explain the differences between pharmacology and pharmacy
pharmacology = branch of medicine concerned with uses, effects and modes of action of drugs pharmacy = how drugs are formulated and dispensed for use as medicines (incl. the law governing medicinal use of drugs)
what us therapeutics?
the medicinal use of drugs to treat or relieve the symptoms of disease (not all drugs are medicine)
what is toxicology?
the branch of pharmacology that focuses on the harmful effect of chemicals, incl. drugs
what is a drug?
a chemical substance of known structure (other than a nutrient/essential dietary ingredient i.e. not vitamins), which when administered to a living organism produces a biological effect
how are drugs named?
drugs used therapeutically usually have at least 3 names: (RS)-2-(d-(2-methylpropyl)phenyl)propanoic acid
chemical name e.g.
common name: ibuprofen
proprietary (trade) names e.g. nurofen (names given by pharmaceutical companies)
how do drugs produce their effects?
- Drugs are exogenous molecules (come from outside the body) that mimic or block the actions of endogenous molecules (molecules found inside the body)
” A drug will not work unless it is bound” Paul Ehrlich
how are drugs grouped?
- they’re usually grouped according to therapeutic use e.g. analgesics, antihypertensives, antibiotics
Or sometimes by mechanism of action e.g. cyclooxygenase inhibitor, beta-blocker
propanolol:
- mechanism of action
- therapeutic use
- property name
- Blocks both beta 1 and beta 2 adrenergic receptors (beta blockers)
- Treat heart problems, help with anxiety and prevent migranes
- Inderal
salbutamol:
1. mechanism of action
2. therapeutic use
3. property name
- selective beta2-adrenergic receptor agonist
- Treat asthma, bronchitis, COPD
- Ventolin
sildenafil
- mechanism of action
- therapeutic use
- property name
- phosphodiesterase inhibitor
- Treats erectile dysfunction
- Revatio/Viagra
fexofenadine
- mechanism of action
- therapeutic use
- property name
- Selective H1-antagonist
- Symptomatic treatment of seasonal allergic rhinitis & chronic idiopathic urticaria
- Allegra
fluoxetine
- mechanism of action
- therapeutic use
- property name
- Selective serotonin reuptake inhibitor
- Treat major depressive disorder, bulimia, OCD etc.
- Prozac
The vast majority of drugs bind to molecular targets that are important proteins within the body. Give examples of some of these target proteins.
- Receptors for neurotransmitters or hormones
- Enzymes
- Ion channels
- Carrier or transport molecules
what are “ligands”?
The small drug molecules that bind to large target proteins
note: Modern computer modelling techniques allow drugs to be designed in silico
- Doesn’t tell you how effective the drugs is, only if it will bind to target protein or not
How well a drug ‘fits’ into its binding site is governed by what?
- the size and flexibility of the drug (steric factors)
How well the drug binds its target protein is determined by what?
- the nature of the chemical bonds that form between the drug molecule and its binding site
do drugs bind reversibly or irreversibly to the target protein? and with what kind of bonds?
- Most drugs (ligands) bind reversibly to the target protein through hydrophobic and hydrogen bonds plus weaker van der waals interactions
- some bind irreversibly through covalent interactions
what is formed when a drug binds to its target protein?
formation of a ligand-protein complex which’ll alter the activity of the protein in some way
what is selectivity in pharmacology and why is it important for drugs to be selective?
- the ability of a drug to affect a particular population
- for drug to be useful therapeutically it must be very selective in its action (e.g. an antihypertensive drug that lowers blood pressure but at same time causes severe GI problems isn’t useful for treating high BP)…shouldn’t cause severe side effects
how can high drug selectivity be achieved?
- design drugs that bind w a high degree of specificity to their target protein. Ideally they will bind ONLY to their target protein & no others
NO drug binds with complete specificity – no drug is free from unwanted side effects
explain the difference between selectivity and specificity in pharmacology
SELECTIVITY – the degree to which a drug acts on a given site relative to other sites
SPECIFICITY – the capacity of a drug to cause a particular action in a population
what is pharmacodynamics (PD)?
defined as “what the drug does to the body” i.e consequence of drug’s actions at a molecular level on the physiology of an organism
what is pharmacokinetics (PK)?
defined as “what the body does to the drug” I.e. how the drug is “handled” by the organism e.g. how it gets to its site of action, how it is metabolised or how its distributed to the different organs
what are the four critical elements of pharmokinetics?
Absorption
Distribution
Metabolism
Excretion
(ADME)
ADME is influenced by
- by the properties of the drug e.g. is the drug in a stable acid environment?
- the characteristics of the person taking the drug e.g. a person who suffers from liver damage will not metabolise a drug as well as a person with a healthy liver
what does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
Importance of absorption in pharmacokinetics?
determines how much and how quickly the drug enters the blood
What influences absorption in pharmacokinetics?
the chemical properties of the drug:
- Its molecular size
- Its lipid solubility, in turn influenced by its ionization (highly charged drugs won’t be dissolved in lipids and s won’t be absorbed across the gut)
- Its chemical stability. Some drugs can’t be taken orally because they aren’t stable in acid environment e.g. of stomach
Importance of distribution in pharmacokinetics?
important to know: where does the drug go after it has been absorbed?
describe distribution in pharmacokinetics
- Usually drugs are distributed around body by circulating in blood plasma and diffusing through tissues dissolved in ECF
- the ability of a drug to dissolve in plasma or ECF is determined by its water (aqueous) solubility
note: when studying drug action we usually measure its concentration in blood plasma, the assumption being that the conc in blood plasma will be related to the conc of drug at its site of action
what are some factors that can interfere with how well a drug is distributed within the body?
Does the patient have adequate circulation?
Does the drug bind to proteins in blood plasma, in particular albumin, drug bound to albumin is “trapped” in the blood (cant leave blood to enter ECF to produce effect)
Does the drug “partition” into body fat stores, drug dissolved in body fat is not active
Can the drug gain access to the organ it acts on e.g. brain is protected by blood brain barrier (BBB) - many drugs struggle to cross BBB
- to quantify impact of these factors we need to measure volume of distribution
what is the volume of distribution?
- volume the drug would occupy if the total amount administered was dissolved in solution at same conc as that found in blood plasma
A drug that acts throughout the body is said to have…what?
“systemic” actions
Give two examples of using knowledge of pharmacokinetics to minimise systemic side effects:
- Local anaesthetics
- non-sedating antihistamines e.g. cetirizine – these drugs relieve hay fever symptoms (e.g. by acting on airways) but don’t cause drowsiness because they’re designed to not cross the BBB
Importance of metabolism and excretion in pharmacokinetics?
These two factors determine how long the effects of a drug last
Drugs are usually metabolised (broken down) in the liver to metabolites which are then excreted by the kidneys
Things in terms of metabolism and excretion in pharmacokinetics?
Does patient have a healthy liver?
How effective are the liver enzymes e.g. genetic differences between patients
Are the metabolites active e.g. codeine is metabolised to morphine
Are the metabolites toxic e.g. paracetamol toxicity is due to a harmful metabolite, not paracetamol itself
Different ways drugs are excreted
most drugs (or at least their metabolites) are excreted in the urine, other routes of excretion include the faeces, sweat, bile and breath
define a drug’s half-life
the time it takes for the amount of a drug’s active substance in your body to reduce by half (in plasma conc)
what is clearance?
the volume of blood plasma cleared of drug in unit time (e.g. ml of plasma per minute)
